Inhibit is a gonadal glycoprotein which preferentially suppresses FSH secretion in vitro and is believed to have a key role in the physiological control of FSH in vivo. Recently, inhibin has been isolated from bovine (Robertson et al 1985 Biochem Biophys Res Comm 126:220; Robertson et al 1986, Mol Cell Endocrinol 44:217; Fukada et al 1986 Mol Cell Endocrinol 44:55), porcine (Miyamoto et al 1985 Biochem Biophys Res Comm 129:396; Ling et al 1985, Proc Nat Acad Sci (USA) 82:7217) and ovine (Leversha et al 1987 J. Endocrinol 113:213) ovarian follicular fluids (FF). The amino acid sequence or porcine (Mason et al 1985 Nature 318:639), bovine (Forage et al 1986 Proc Nat Acad Sci (USA) 83:3091), human (Mason et al 1986 Biochem Biophys Res Comm 135:957; Steward et al 1986 FEBS 206:329), ovine (Crawford et al 1987 Mol Endocrinol 1:699; Forage et al 1987 Serono Symposium 42:89) and rat (Esch et al 1987 Mol Endocrinol 1:388; Woodruff et al 1987 Mol Endocrinol 1:561) inhibin has been determined by cloning techniques. Inhibit in a dimer of two partially homologous subunits (.alpha. and .beta.) joined by disulphide bonds. Inhibin with two variants of the .beta. subunit (A and B) has been isolated from porcine FF (Ling et al 1985 Proc Nat Acad Sci (USA) 82:7217) and their mRNAs also identified in the human (Mason et al 1986 Biochem Biophys Res Comm 135:957; Steward et al 1987 FEBS 206:329) and rat (Esch et al 1987 Mol Endocrinol 1:949; Woodruff et al 1987 Mol Endocrinol 1:561). Inhibin has also been isolated as two molecular weight forms (58000D and 31-32000D) which differ in the extent of processing of the .alpha. chain (Robertson et al 1986 Mol Cell Endocrinol 44:271). Bovine 58 kD inhibin is cleave to 31 kD inhibin in the presence of serum but not follicular fluid (McLachlan et al 1986 Mol Cell Endocrinol 46:175) suggesting that processing of the .alpha. subunit is extragonadal. Inhibin has also been identified as a placental product in rats and humane (McLachlan et al 1985 Biochem Biophys Res Comm 140:485; Petraglia et al 1987 Science 237:187), suggesting that it plays a role in pregnancy.
Recently, several proteins have been isolated from gonadal and other tissues and found to be structurally related to inhibin particularly to the .beta. subunit, but with different biological activities. These proteins include activin-A and activin-AB (inhibin .beta.A.beta.A or .beta.A.beta.B subunit dimers, Vale et al 1986 Nature 321:776; Ling et al 1986 Nature 321:779) or erythroid differentiating factor (Eto et al 1987 Biochem Biophys Res Comm 142:1095); Mullerian inhibitory substance (Cate et al 1986, Cell 45:685) and transforming growth factor-.beta. (Sporn et al 1987 J Cell Biol 105:1039). TGF-` is a potent inhibitor of lectin-induced T lymphocyte proliferation in vitro, and many patients with glioblastomas, which secrete large amounts of TGF-.beta., display suppressed immune functions (Kherl et al 1986 J Exp Med 163:1037; Wrann et al 1987 EMBO 6:1633).